8 USE IN SPECIFIC POPULATIONS
Available human data on the use of RELPAX in pregnant women are not sufficient to draw conclusions about drug-associated risk for major birth defects and miscarriage. In animal studies, oral administration of eletriptan during pregnancy or throughout pregnancy and lactation was associated with developmental toxicity (decreased fetal and pup weights, increased incidences of fetal structural abnormalities, decreased pup viability) at clinically-relevant doses [see Data].
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine.
A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for triptans before pregnancy only. Of the 189 women who redeemed prescriptions for eletriptan during the first trimester, 4 (2.1%) had infants with major congenital malformations, while for the 174 women who redeemed prescriptions for eletriptan before, but not during, pregnancy, 11 (6.3%) had infants with major congenital malformations. Methodological limitations of this study, including small size of the eletriptan population and infrequent events, do not allow for thorough characterization of risk.
When pregnant rats were administered eletriptan (0, 10, 30, or 100 mg/kg/day) during the period of organogenesis, fetal weights were decreased and the incidences of vertebral and sternebral variations were increased at 100 mg/kg/day (approximately 12 times the maximum recommended human dose [MRHD] of 80 mg/day on a mg/m2 basis). The 30 and 100 mg/kg/day doses were also maternally toxic, as evidenced by decreased maternal body weight gain during gestation. The no-effect dose for adverse effects on embryofetal development in rats was 30 mg/kg/day, which is approximately 4 times the MRHD on a mg/m2 basis.
When eletriptan (0, 5, 10, or 50 mg/kg/day) was orally administered to pregnant rabbits throughout organogenesis, fetal weights were decreased at 50 mg/kg/day. The incidences of fused sternebrae and vena cava deviations were increased at all doses. Maternal toxicity was not evident at any dose. A no-effect dose for adverse effects on embryofetal development in rabbits was not established; the lowest dose tested (5 mg/kg/day) is similar to the MRHD on a mg/m2 basis.
Oral administration of eletriptan (0, 5, 15, or 50 mg/kg/day) to female rats throughout pregnancy and lactation resulted in a decrease in offspring viability and body weight at the highest dose tested. The no-effect dose for adverse effects on pre- and postnatal development in rats (15 mg/kg/day) is approximately 2 times the MRHD on a mg/m2 basis.
Eletriptan is excreted in human milk. There are no data on the effects of eletriptan on the breastfed infant or the effects of eletriptan on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for RELPAX and any potential adverse effects on the breastfed child from RELPAX or from the underlying maternal condition. Infant exposure can be minimized by avoiding breastfeeding for 24 hours after treatment.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
The efficacy of RELPAX Tablets (40 mg) in patients 11–17 was not established in a randomized, placebo-controlled trial of 274 adolescent migraineurs [see Clinical Studies (14)]. Adverse reactions observed were similar in nature to those reported in clinical trials in adults. Postmarketing experience with other triptans includes a limited number of reports that describe pediatric patients who have experienced clinically serious adverse reactions that are similar in nature to those reported rarely in adults. Long-term safety of eletriptan was studied in 76 adolescent patients who received treatment for up to one year. A similar profile of adverse reactions to that of adults was observed. The long-term safety of eletriptan in pediatric patients has not been established.
8.5 Geriatric Use
Blood pressure was increased to a greater extent in elderly subjects than in young subjects. The pharmacokinetic disposition of eletriptan in the elderly is similar to that seen in younger adults [see Clinical Pharmacology (12.3)]. In clinical trials, there were no apparent differences in efficacy or the incidence of adverse reactions between patients under 65 years of age and those 65 and above.
8.6 Hepatic Impairment
The effect of severe hepatic impairment on RELPAX metabolism has not been evaluated. RELPAX is not recommended for use in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].